miR-486 is involved in the pathogenesis of acute myeloid leukemia by regulating JAK-STAT signaling.

Acute myeloid leukemia (AML) is a widely prevalent disease worldwide and poses a large threat to public health. Previous studies have shown that AML is associated with cytogenetic heterogeneity, complex subtypes, and different therapeutic approaches. In this study, we found that miR-486 was upregulated in AML using both The Cancer Genome Atlas (TCGA) database and patient tissues. After knockdown of miR-486 by short hairpin RNA (shRNA), we discovered that miR-486 was required for cell proliferation. Through miRNA profile analysis and a dual-luciferase reporter assay, suppressor of cytokine signaling 2 (SOCS2) was identified as a direct target of miR-486. Therefore, by silencing SOCS2, a negative regulator of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, miR-486 enhanced JAK-STAT3 activity and promoted cell proliferation. The miR-486-SOCS2-STAT3 proliferation axis is therefore involved in the pathogenesis of AML, providing a novel molecular mechanism and diagnostic and therapeutic clues for AML.

A novel MEF2C mutation in lymphoid neoplasm diffuse large B-cell lymphoma promotes tumorigenesis by increasing c-JUN expression.

Diffuse large B-cell lymphoma (DLBCL) is the most aggressive non-Hodgkin lymphoma (NHL), accounting for about 31% of the newly diagnosed NHL worldwide. Although approximately 60% of patients who initially received a standard R-CHOP treatment likely have a 3-year event-free survival, many patients become refractory or relapsed due to the genetic heterogeneity of this malignancy. Hence, new treatment strategies are urgently needed. MEF2C, a member of the MEF2 transcription factor family gene, plays great important roles involved in the development of various tissues and the pathogenesis of lymphoma. However, the exact functions and molecular mechanisms of MEF2C in DLBCL are not fully investigated. By Sanger sequencing, we identified a novel point mutation of MEF2C at the p.N389 site in DLBCL patient, which was further validated by several DLBCL cell lines. Intriguingly, we found that the p.N389S mutation did not influence MEF2C expression, protein stability, and subcellular distribution, but enhanced its transcriptional activity. Furthermore, we demonstrated that MEF2C p.N389S mutation promotes DLBCL cell proliferation, cellular adhesion, and tumor formation in nude mice. On mechanism, our data revealed that MEF2C p.N389S mutation increases c-JUN expression, and c-JUN regulation mediated the oncogenic function of MEF2C p.N389S mutation on DLBCL cells. Our finding may provide a significant insight into the DLBCL and a compelling therapy target for this disease treatment.

Predicting mutant selection in competition experiments with ciprofloxacin-exposed Escherichia coli.

Predicting competition between antibiotic-susceptible wild-type (WT) and less susceptible mutant (MT) bacteria is valuable for understanding how drug concentrations influence the emergence of resistance. Pharmacokinetic/pharmacodynamic (PK/PD) models predicting the rate and extent of takeover of resistant bacteria during different antibiotic pressures can thus be a valuable tool in improving treatment regimens. The aim of this study was to evaluate a previously developed mechanism-based PK/PD model for its ability to predict in vitro mixed-population experiments with competition between Escherichia coli (E. coli) WT and three well-defined E. coli resistant MTs when exposed to ciprofloxacin. Model predictions for each bacterial strain and ciprofloxacin concentration were made for in vitro static and dynamic time-kill experiments measuring CFU (colony forming units)/mL up to 24 h with concentrations close to or below the minimum inhibitory concentration (MIC), as well as for serial passage experiments with concentrations well below the MIC measuring ratios between the two strains with flow cytometry. The model was found to reasonably well predict the initial bacterial growth and killing of most static and dynamic time-kill competition experiments without need for parameter re-estimation. With parameter re-estimation of growth rates, an adequate fit was also obtained for the 6-day serial passage competition experiments. No bacterial interaction in growth was observed. This study demonstrates the predictive capacity of a PK/PD model and further supports the application of PK/PD modelling for prediction of bacterial kill in different settings, including resistance selection.

Warburg Effects in Cancer and Normal Proliferating Cells: Two Tales of the Same Name / 基因组蛋白质组与生物信息学报·英文版

It has been observed that both cancer tissue cells and normal proliferating cells (NPCs) have the Warburg effect. Our goal here is to demonstrate that they do this for different reasons. To accomplish this, we have analyzed the transcriptomic data of over 7000 cancer and control tissues of 14 cancer types in TCGA and data of five NPC types in GEO. Our analyses reveal that NPCs accumulate large quantities of ATPs produced by the respiration process before starting the Warburg effect, to raise the intracellular pH from ∼6.8 to ∼7.2 and to prepare for cell division energetically. Once cell cycle starts, the cells start to rely on glycolysis for ATP generation followed by ATP hydrolysis and lactic acid release, to maintain the elevated intracellular pH as needed by cell division since together the three processes are pH neutral. The cells go back to the normal respiration-based ATP production once the cell division phase ends. In comparison, cancer cells have reached their intracellular pH at ∼7.4 from top down as multiple acid-loading transporters are up-regulated and most acid-extruding ones except for lactic acid exporters are repressed. Cancer cells use continuous glycolysis for ATP production as way to acidify the intracellular space since the lactic acid secretion is decoupled from glycolysis-based ATP generation and is pH balanced by increased expressions of acid-loading transporters. Co-expression analyses suggest that lactic acid secretion is regulated by external, non-pH related signals. Overall, our data strongly suggest that the two cell types have the Warburg effect for very different reasons.

[Applied anatomy of supraclavicular artery island flap and preliminary clinical report on reconstruction of tongue].

OBJECTIVE: To study the anatomy of supraclavicular artery island flap and report the clinical application of the island flap for the reconstruction of tongue defects. METHODS: The branch, origination, course, length and diameter of transverse cervical artery and supraclavicular artery were observed on 20 flaps of 10 adult cadavers perfused with lead oxide-gel, and the draining veins were also observed. The supraclavicular artery island flaps were used to reconstruct the defects following tongue cancer ablation in 4 patients, and the data concerning functional impairment, aesthetic outcome and donor site morbidity were analyzed. RESULTS: The transverse cervical artery were originated from the thyrocervical trunk or subclavical artery, and separated into deep branch and superficial branch above the middle third of the clavicle. The supraclavicular artery were originated from superficial branch of the transverse cervical artery and extended to backward and outward, and run over surface of trapezius, acromial end of clavicle and deltoid fascia, and then penetrated the deep fascia and go into skin and subcutaneous tissue of supraclavicular and shoulder regions. The distance between the origins of the supraclavicular and transverse cervical arteries was on average 4.3 cm, and the distance between the origin of supraclavicular artery and the point where it penetrated the deep fascia was on average 3.6 cm. The external diameter of the transverse cervical artery was on average 2.7 mm, and the external diameter of supraclavicular artery was on average 1.1 mm. Two supraclavicular comitant veins ran adjacent to the supraclavicular artery and drained into the transverse cervical vein and external jugular vein respectively. In the clinical study, 3 flaps survived completely and part of the skin paddle of the flap in one case exhibited necrosis. The contour and function of tongues were restored well and there was no limitation of shoulder motion in all 4 cases. CONCLUSIONS: The supraclavicular artery island flap with supraclavicular artery as nutrient vessel is reliable for reconstruction of oral, maxillofacial and neck defects, and it can be used as a free flap equipped with the transverse cervical artery.

Applied anatomy of supraclavicular artery island flap and preliminary clinical report on reconstruction of tongue / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To study the anatomy of supraclavicular artery island flap and report the clinical application of the island flap for the reconstruction of tongue defects.</p><p><b>METHODS</b>The branch, origination, course, length and diameter of transverse cervical artery and supraclavicular artery were observed on 20 flaps of 10 adult cadavers perfused with lead oxide-gel, and the draining veins were also observed. The supraclavicular artery island flaps were used to reconstruct the defects following tongue cancer ablation in 4 patients, and the data concerning functional impairment, aesthetic outcome and donor site morbidity were analyzed.</p><p><b>RESULTS</b>The transverse cervical artery were originated from the thyrocervical trunk or subclavical artery, and separated into deep branch and superficial branch above the middle third of the clavicle. The supraclavicular artery were originated from superficial branch of the transverse cervical artery and extended to backward and outward, and run over surface of trapezius, acromial end of clavicle and deltoid fascia, and then penetrated the deep fascia and go into skin and subcutaneous tissue of supraclavicular and shoulder regions. The distance between the origins of the supraclavicular and transverse cervical arteries was on average 4.3 cm, and the distance between the origin of supraclavicular artery and the point where it penetrated the deep fascia was on average 3.6 cm. The external diameter of the transverse cervical artery was on average 2.7 mm, and the external diameter of supraclavicular artery was on average 1.1 mm. Two supraclavicular comitant veins ran adjacent to the supraclavicular artery and drained into the transverse cervical vein and external jugular vein respectively. In the clinical study, 3 flaps survived completely and part of the skin paddle of the flap in one case exhibited necrosis. The contour and function of tongues were restored well and there was no limitation of shoulder motion in all 4 cases.</p><p><b>CONCLUSIONS</b>The supraclavicular artery island flap with supraclavicular artery as nutrient vessel is reliable for reconstruction of oral, maxillofacial and neck defects, and it can be used as a free flap equipped with the transverse cervical artery.</p>